The present invention relates to the treatment of respiratory disorders. More specifically, the present invention relates to the treatment of poor respiratory muscle function.
Due to a number of disease states, and other disorders, many patients present poor respiratory muscle function. Respiratory-muscle fatigue can result in carbon dioxide retention in patients and can be the result of respiratory disease, malnutrition, neuromuscular disorder, or other abnormal states. Respiratory-muscle fatigue can result in hypercapnia and in ventilatory failure.
Fatigue of the diaphragm has been defined as an inability to continue generating a sufficient pressure to maintain adequate alveolar ventilation. The failure to maintain adequate ventilation results when the tension produced by the diaphragm consistently exceeds 40 percent of the maximal level. Additionally, fatigue of the respiratory muscles occurs when mouth pressure consistently exceeds 50 to 70 percent of maximal levels that can be generated. Roussos, C., Macklem, P.T., The Respiratory Muscles, New England Journal of Medicine 1982; 307: 786-97.
Respiratory-muscle fatigue is believed to develop when the energy requirements of the diaphragm muscles exceed the energy supply. Weinberger et al, Hypercapnia, The New England Journal of Medicine, 1989; 321: 1223-1231. A number of factors can increase energy demands, or decrease available energy, increasing the likelihood of muscle fatigue. For example, low cardiac output, anemia, and decreased oxygen saturation can result in decreased energy supply and therefore an increased likelihood of respiratory-muscle fatigue. With respect to an increase in energy demands, this can occur due to high levels of ventilation or an increase in the breathing effort, for example, increased resistance to air flow or decreased compliance of the respiratory system.
Additionally, factors that decrease muscle strength can also predispose a patient to respiratory muscle fatigue. Therefore, respiratory muscle fatigue can be associated with primary neuromuscular disease, malnutrition, or electrolyte alterations, for example, hypokalemia and hypophosphatemia can cause substantial weakness of the respiratory muscles and contribute to or precipitate hypercapnic ventilatory failure.
Pharmaceutical intervention to improve diaphragmatic function has been proposed. Theophylline and sympathomimetic agents have been suggested as theoretically improving diaphragmatic function; But, their clinical utility in this regard is controversial. Moxham, Aminophylline and the Respiratory Muscles: an Alternative View, Clinical Chest Medicine 1988; 9:325-36. Diaphragmatic rest using a mechanical ventilatory support has been used in patients wherein respiratory muscle fatigue has contributed to hypercapnic respiratory fatigue. Peters, et al, Home Mechanical Ventilation, Mayo Clinic Procedure, 1988; 63:1208-13.